Potassium Carbonate → HCID 59332603, compound

HRID 656155Notes

Reaction equation

HRID 656155 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[C@@H:14]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[C@@H:16]([CH:22]([CH3:24])[CH3:23])[CH2:15]1.O1CCOCC1.[S:31]1[CH:35]=[CH:34][CH:33]=[C:32]1B(O)O.C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH3:23][CH:22]([C@H:16]1[CH2:15][C@H:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:32]4[S:31][CH:35]=[CH:34][CH:33]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:19][CH2:18][S:17]1(=[O:21])=[O:20])[CH3:24]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27339602-Thiopheneboronic acidHCID 66746207HCID 66746207, compound

Product 1

HCID 59332603HCID 59332603, compoundYield 21.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

(racemic)-5-Bromo-3-[trans-2-(1-methylethyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]-1H-indole-7-carboxamide (60 mg, 0.145 mmol) was placed in a microwave vial and dissolved with 1,4-Dioxane (2 mL) and Water (1.000 mL). 2-Thienylboronic acid (37.1 mg, 0.290 mmol) and K2CO3 (60.2 mg, 0.435 mmol) were added. Argon was bubbled in the mixture for 10 min with stirring, PdCl2(dppf) (5.60 mg, 0.012 mmol) was added, and argon was bubbled another 10 mins. The vial was sealed and put under microwave 5 mins at 100° C. with high absorption parameter. The reaction was complete after the microwave treatment. The crude was run through a thiol-SPE cartridge eluting with 2 mL of methanol and the eluted solvents are evaporated. The brown oil was dissolved in 2-3 mL of DMSO, and purified on a Gilson HPLC. The desired fractions were concentrated, giving 13 mg of the title compound.

Workup

  1. customArgon was bubbled in the mixture for 10 min
  2. customargon was bubbled another 10 mins
  3. customThe vial was sealed
  4. washeluting with 2 mL of methanol
  5. customthe eluted solvents are evaporated
  6. dissolutionThe brown oil was dissolved in 2-3 mL of DMSO
  7. custompurified on a Gilson HPLC
  8. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-cc448651855145039d78901557552585
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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